The impact of Omicron variants on cirrhosis was largely unknown. Herein, we aimed to evaluate the impact of SARS-CoV-2 omicron variants infection on the clinical course and mortality of patients with liver cirrhosis.

Between 26 December 2022, and 27 January 2023, eighty-two hospitalized patients with cirrhosis and confirmed SARS-CoV-2 infection were enrolled. The clinical and pulmonary CT imaging features were retrospectively collected. A gender and age-matched cohort of 51 non-cirrhotic patients with COVID-19 were also included.

Our results indicated the symptom heterogeneity in patients with cirrhosis infected with omicron variants. Patients with more severe liver disease tended to have less severe respiratory symptoms and less pulmonary lesions. SARS-CoV-2 omicron did not cause obvious perturbation of liver function or cirrhosis decompensation. In comparison with hospitalized COVID-19 patients without liver cirrhosis, cirrhotic patients showed more severe pulmonary lesions and higher levels of inflammatory cytokine IL-6, but no significant increase in mortality. Multivariate analysis identified lung lesions proportion, MELD ≥ 15 score, and APTT as independent predictors for 28-day-mortality in these patients.

SARS-CoV-2 omicron variants caused a more severe inflammatory response in cirrhotic patients than in non-cirrhotic patients, but no further deterioration of liver function. Instead, patients with advanced stage of liver cirrhosis showed milder respiratory symptoms and pulmonary lesions. These results underscore the intricate relationship between Omicron infection and cirrhosis, highlighting the necessity for personalized clinical approaches in managing this specific patient group.

Despite azvudine being prioritized for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, its effectiveness and safety remain inadequately substantiated in hospitalized SARS-CoV-2 infected patients with liver diseases. A retrospective nine-center cohort study along with an independent validation cohort is conducted to examine the efficacy of azvudine (Clinical Trial Registration Number: NCT06349655). The primary outcome is all-cause mortality and the secondary outcome is composite disease progression. Efficacy is assessed via Kaplan-Meier analysis and Cox regression, with subgroup and sensitivity analyses for further validation. Among 32 864 hospitalized SARS-CoV-2 infected patients, 1022 eligible azvudine recipients, and 1022 controls are included through propensity score match. Kaplan-Meier analysis reveals that azvudine treatment is associated with a lower risk of all-cause mortality and composite disease progression (both p<0.0001). Cox regression analysis suggests azvudine recipients could have a 39% lower risk of all-cause mortality than controls (95% confidence interval [CI]: 0.468-0.795, p<0.001), but with no notable significance in composite disease progression (hazard ratio: 0.85, 95% CI: 0.686-1.061, p = 0.154). Subgroup analysis suggests that azvudine has a greater benefit for both all-cause mortality and composite disease progression in patients with kidney diseases or without autoimmune diseases. Three sensitivity analyses and validation cohorts confirm the robustness of the findings. Safety analysis observes few adverse events in azvudine recipients. Within 15 days after azvudine administration, no significant difference in liver function indexes and kidney function indexes is observed between the two groups except for a few time points. These findings demonstrate that azvudine shows potential clinical efficacy in improving all-cause mortality in hospitalized SARS-CoV-2 infected patients with liver diseases, with acceptable adverse effects.

Patients with liver cirrhosis are at an increased risk of mortality from coronavirus disease 2019 (COVID-19). Remdesivir, an adenosine analog, exhibits activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is thus recommended for inpatients with COVID-19. This study evaluated the effectiveness and safety of remdesivir in patients with COVID-19 and liver cirrhosis.

This retrospective study was conducted using data from Taiwan's largest healthcare system. The study cohort comprised adult patients with COVID-19 and liver cirrhosis who visited our emergency department between April 2021 and September 2022. Remdesivir's adverse effects, including bradycardia, anemia, unstable glucose levels, and abnormal liver function test results, were recorded. Treatment outcomes were assessed in terms of hospitalization duration, mortality, intubation, and intensive care unit admission.

This study included 1368 patients with COVID-19 and liver cirrhosis, of whom 46 received remdesivir. Remdesivir recipients were older (66.5 vs. 62 years; p = 0.042) and had a higher rate of oxygen therapy use (56.52% vs. 32.22%; p = 0.001) than nonrecipients. Common adverse effects of remdesivir included lower heart rates (83 vs. 96 bpm; p < 0.001) and decreased hemoglobin levels (9.5 vs. 10.2 g/dL; p = 0.003) without fatal consequences. No statistically significant difference between remdesivir recipients and nonrecipients in hospitalization duration, intubation rates, or mortality rates was found.

Remdesivir is safe for treating COVID-19 in patients with liver cirrhosis. Although remdesivir recipients exhibited trends toward improved outcomes in our study, large-scale studies are required to confirm its efficacy in this population.

The potential effect of ursodeoxycholic acid (UDCA) on the clinical outcomes of SARS-CoV-2 in patients with chronic liver diseases has been a subject of ongoing debate since the onset of the SARS-CoV-2 pandemic in 2019. This study aims to investigate the effect of UDCA on the prognosis of SARS-CoV-2 infection in patients with chronic liver diseases.

A total of 926 patients with chronic liver diseases who contracted their first SARS-CoV-2 infection during December 2022 to January 2023, were included in this study. Participants were divided into two groups based on the use of UDCA: the UDCA cohort (n = 329) and the non-UDCA cohort (n = 597). After performing a 1:1 age-and sex-matching, the analysis proceeded with 309 patients from each group for further evaluation.

In the UDCA-treated cohort, the incidence of asymptomatic SARS-CoV-2 infections was significantly higher, with 30.1% of patients affected, compared to 6.47% in the non-UDCA group (p < 0.0001). Multivariable analysis identified UDCA as a protective factor against symptomatic infections, yielding an odds ratio (OR) of 4.77 (95% CI: 2.70-8.44, p < 0.001). Furthermore, age over 50 was found to be a risk factor for asymptomatic infections in the UDCA cohort, with an adjusted OR of 1.51 (95% CI: 1.01-2.24, p = 0.05).

The study suggests that UDCA therapy may improve clinical outcomes in patients with chronic liver diseases patients who are infected with SARS-CoV-2, highlighting its potential role in improving prognosis within this vulnerable population. However, further research is required to validate these findings and to elucidate the mechanisms underlying UDCA's protective effect.

The liver is the target of various viruses that can cause significant damage, impair function and potentially threaten a patient's life. While the "alphabetic" hepatitis viruses A, B, C, D, and E are well-characterized, and their impact on liver function well-documented, many emerging and re-emerging viruses, some of which are considered by the WHO to be potential pandemic threats, also infect the liver. In this review, we describe the current state of knowledge regarding liver infections caused by major non-alphabetic hepatotropic viruses and their effects on liver functions.

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the 'Golden Therapeutic Window', the 'transplant window', and plasmapheresis as a treatment modality. Also, the data has been key to identifying pediatric ACLF. The European Association for the Study of Liver-Chronic Liver Failure (EASL CLIF) and the North American Association for the Study of the End Stage Liver Disease (NACSELD) from the West added the concepts of organ failure and infection as precipitants for the development of ACLF and CLIF-Sequential Organ Failure Assessment (SOFA) and NACSELD scores for prognostication. The Chinese Group on the Study of Severe Hepatitis B (COSSH) added COSSH-ACLF criteria to manage hepatitis b virus-ACLF with and without cirrhosis. The literature supports these definitions to be equally effective in their respective cohorts in identifying patients with high mortality. To overcome the differences and to develop a global consensus, APASL took the initiative and invited the global stakeholders, including opinion leaders from Asia, EASL and AASLD, and other researchers in the field of ACLF to identify the key issues and develop an evidence-based consensus document. The consensus document was presented in a hybrid format at the APASL annual meeting in Kyoto in March 2024. The 'Kyoto APASL Consensus' presented below carries the final recommendations along with the relevant background information and areas requiring future studies.

The impact of coronavirus disease 2019 (COVID-19) on patients with acute-on-chronic liver failure (ACLF) remains unclear. To investigate the clinical characteristics of patients with ACLF complicated with COVID-19 in order to provide evidence for the precise treatment of this patient population.

A total of 34 ACLF patients with COVID-19 admitted to these three hospitals from December 2022 to August 2023 were included as the ACLF+COVID-19 group. Additionally, 34 age-, gender-, etiology-, and Model for End-Stage Liver Disease-Sodium (MELD-Na) score-matched ACLF patients were screened from 286 ACLF patients as the ACLF group. From 382 COVID-19 patients, 34 were selected as the COVID-19 group, matching the ACLF+COVID-19 group in age, gender, and illness severity. Clinical features of these three groups were compared, with the primary measure being the 28-day mortality rate in the ACLF patients and the secondary measures including clinical symptoms, laboratory tests, comorbidities, and complications in three groups.

Compared with the ACLF group, the ACLF+COVID-19 group had significantly higher incidence rates of fever, cough, sputum production, fatigue, and hypoxemia (all p<0.01). Patients in the ACLF+COVID-19 group were more likely to have hepatic encephalopathy (p=0.015), lower platelet count (p=0.016) and elevated IL-6 level (p=0.026), and higher MELD-Na score (p=0.041) one week after admission, but without a significant increase in 28-day mortality rate (p=0.16).

ACLF patients with COVID-19 have increased risk for thrombocytopenia, more obvious inflammatory response, and rapid disease progression 1 week after admission, but the 28-day mortality rate is similar to that of ACLF patients without COVID-19.

Chronic liver disease (CLD) has massive systemic repercussions including major impacts on the body's immune system. Abnormalities in phenotype, function and numbers of various immune cell subsets have been established by a large number of clinical and pre-clinical studies. The loss of essential immune functions renders CLD-patients exceptionally susceptible to bacterial and viral infections and also impairs the efficacy of vaccination. Consequently, infections represent a major clinical issue causing significant morbidity and mortality in these patients. Mechanistically, the immune dysfunction associated with CLD results from the increased translocation of bacteria and bacterial cues from the intestine. These trigger a signaling axis around the cytokines IFN I and IL-10 in hepatic myeloid cells, which aside from impairing the function of the myeloid cells themselves, also has notable negative impacts on the functionality of other immune cells. T cells in CLD-patients and -models are especially affected by this signaling axis and display a variety of quantitative and qualitative defects. Due to the high clinical relevance, understanding the mechanisms underlaying CED-associated immune dysfunction is of critical importance to discover and develop new therapeutic targets.

The effects of a concomitant infection of hepatitis B virus (HBV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are still debated, with a recognized major risk of HBV reactivation during immune-suppressive treatments. The aim of this study was to determine the prevalence and predictive factors of HBV reactivation in a cohort of hospitalized patients with coronavirus disease 2019 (COVID-19) and a current or past hepatitis B infection. In a monocentric retrospective observational study, we enrolled all consecutive hospital admitted patients with COVID-19 pneumonia and a positive HBV serology (N = 84) in our Infectious Diseases Unit from April 2021 to December 2023. We identified 18 (21%) HBsAg-positive/anti-HBc-positive, 41 (49%) HBsAg-negative/anti-HBc-positive/anti-HBs-positive, and 25 (30%) HBsAg-negative/anti-HBc-positive/anti-HBs-negative subjects. The overall rate of hepatitis flare was 10.7%, without any HBsAg seroreversion, severe HBV reactivation, and/or need for new HBV antiviral therapy introduction. Systemic corticosteroid treatment for COVID-19 and baseline anti-HBsAg status were associated with this risk of HBV reactivation. In conclusion, the overall risk of hepatitis flares in hospitalized COVID-19 was reasonably low, with higher doses of corticosteroids treatment being the major risk factor for HBV reactivation, and anti-HBs-positive serological status as a protective element.

Plants are crucial medicinal resources, with 80 % of people relying on them for primary healthcare. The search for natural antiviral compounds is increasing, especially in semi-arid ecosystems where abiotic stress promotes the production of beneficial secondary metabolites. This review highlights semi-arid plants with the potential as functional foods to combat viral diseases and other illnesses. Literature was searched in databases like ScienceDirect to gather information on novel compounds from stress-tolerant semi-arid plant species. These compounds have potential uses in treating viral infections and other health issues such as diabetes and high blood pressure. The review screened 61 semi-arid plants known for their antiviral metabolites. Eight plants were identified with novel antiviral compounds. Key metabolites include agathisflavone, pectic arabinogalactan, azadirachtin, aloin, aloe-emodin, aloesaponarin I, allicin, terpenoids, chlorogenic acids, curcumin, chromones, β-sitosterol, lupeol, oleuropein, carissol, β-amyrin, and ∆-9-tetrahydrocannabinol. Stress-tolerant semi-arid plants are significant sources of metabolites for treating infectious diseases and boosting immune systems. Further research on these metabolites in animal models is needed to verify their efficacy for treating human diseases during endemic and pandemic outbreaks, such as COVID-19.

Patients with cirrhosis are known to be prone to infections. Infections can trigger organ failures and decompensations in cirrhosis. Septic shock can increase mortality by fourfold and cause hemodynamic imbalances, adding to the already hyperdynamic circulation. Management of septic shock in cirrhosis can be tricky due to this complex interplay of altered hemodynamics, immune function, and coagulation.

In this review, we explore the pathophysiological basis, screening, monitoring and management of septic shock in cirrhosis. We also explore novel biomarkers, the growing challenge of multidrug-resistant pathogens and novel and adjunctive therapies. Finally, we propose an algorithm for the management of septic shock in cirrhosis. We conducted a comprehensive search of electronic databases such as PubMed, Web of Science, and Cochrane Library using the keywords and MeSH terms like 'septic shock,' 'cirrhosis,' 'liver disease,' 'sepsis' among others. The search was restricted to peer-reviewed articles in English.

The difficulties in managing septic shock in cirrhosis are discussed, emphasizing personalized approaches over protocol-driven care. Fluid and vasopressor management, antibiotic timing and selection, the role of adjunctive therapies, the importance of lactate clearance, gut failure, and the need for further research in this population are highlighted.

Longitudinal analysis of antibody responses following three-dose COVID-19 vaccination in patients with chronic liver disease (CLD) has been limited. From August 2021 to February 2023, sequential anti-SARS-CoV-2 spike IgG titers were determined in 45 patients with CLD who received two or three doses of COVID-19 vaccine. The geometric mean of anti-spike IgG at four weeks after the second and third doses were 1313.16 BAU/mL and 3042.29 BAU/mL, respectively, and it decreased significantly from four to 24 weeks after the second (1313.16 vs. 198.42 BAU/mL, p = 0.002) and the third (3042.29 vs. 636.71 BAU/mL, p < 0.001) dose. The anti-spike IgG titers in participants receiving prime-boost homologous mRNA vaccines (BNT162b2 or mRNA-1273) were comparable between participants with and those without significant liver fibrosis at each follow-up time point. This study demonstrated a notable decrease in anti-spike IgG after completion of the vaccination schedule in patients with CLD, highlighting the importance of additional booster doses.

This review explores the mechanisms, diagnostic approaches, and management strategies for COVID-19-induced liver injury, with a focus on its impact on patients with pre-existing liver conditions, liver cancer, and those undergoing liver transplantation.

A comprehensive literature review included studies on clinical manifestations of liver injury due to COVID-19. Key areas examined were direct viral effects, drug-induced liver injury, cytokine storms, and impacts on individuals with chronic liver diseases, liver transplants, and the role of vaccination. Data were collected from clinical trials, observational studies, case reports, and review literature.

COVID-19 can cause a spectrum of liver injuries, from mild enzyme elevations to severe hepatic dysfunction. Injury mechanisms include direct viral invasion, immune response alterations, drug toxicity, and hypoxia-reperfusion injury. Patients with chronic liver conditions (such as alcohol-related liver disease, nonalcoholic fatty liver disease, cirrhosis, and hepatocellular carcinoma) face increased risks of severe outcomes. The pandemic has worsened pre-existing liver conditions, disrupted cancer treatments, and complicated liver transplantation. Vaccination remains crucial for reducing severe disease, particularly in chronic liver patients and transplant recipients. Telemedicine has been beneficial in managing patients and reducing cross-infection risks.

This review discusses the importance of improved diagnostic methods and management strategies for liver injury caused by COVID-19. It emphasizes the need for close monitoring and customized treatment for high-risk groups, advocating for future research to explore long-term effects, novel therapies, and evidence-based approaches to improve liver health during and after the pandemic.

The impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC) remains uncertain given the lack of sufficient evidence.

To investigate the impact of prior SARS-CoV-2 infection on postoperative recovery of patients who underwent liver resection for hepatocellular carcinoma (HCC).

Patients who were pathologically diagnosed with HCC and underwent elective partial hepatectomy in Guangdong Provincial People's Hospital between January 2022 and April 2023 were enrolled in this retrospective cohort study. The patients were divided into two groups based on their history of SARS-CoV-2 infection. Rehabilitation parameters, including postoperative liver function, incidence of complications, and hospitalization expenses, were compared between the two groups. Propensity score matching (PSM) was performed to reduce confounding bias.

We included 172 patients (58 with and 114 without prior SARS-CoV-2 infection) who underwent liver resection for HCC. No significant differences in the rehabilitation parameters were observed between the two groups. After PSM, 58 patients were selected from each group to form the new comparative groups. Similar results were obtained within the population after PSM.

Prior SARS-CoV-2 infection does not appear to affect postoperative rehabilitation, including liver function, postoperative complications, or hospitalization expenses among patients with HCC after elective partial hepatectomy.

Liver function test (LFT) abnormalities are higher in patients with severe COVID-19. Most of the studies on this theme were conducted in foreign nations, and the association with LFT abnormalities was not sufficiently addressed in the study areas. Therefore, the current study aimed to investigate the effects of COVID-19 infection on liver function of patients.

A facility-based comparative cross-sectional study was carried out from 10 April to 15 June 2022, among COVID-19 infected individuals admitted in Eka Kotebe General Hospital and Saint Petrous Specialized Hospitals, Addis Ababa, 2022.

A total of 284 confirmed COVID-19-positive and COVID-19-negative controls matched by gender and age were included in the present study.

Among SARS-COV-2 positive groups, 63 (44.4%) had one or more LFT abnormalities. The most common elevated level of the LFTs among patients with COVID-19 were gamma-glutamyl transferase (GGT) 50 (35.2%), while the most common lowered level was albumin 58 (40.8%). The mean values of aspartate aminotransferase (AST) (35.4±26.9 vs 22.9±12.6, p<0.001) were significantly different between patients with COVID-19 and the COVID-19-free groups. Being COVID-19-positive was significantly associated with an elevated level of AST (AOR=3.0, 95% CI 1.2 to 7.4) and GGT (AOR=4.55, 95% CI 2.02 to 10.3). Being male was significantly associated with an elevated level of total bilirubin (BILT, AOR=2.41, 95% CI 1.2 to 4.9) and direct bilirubin (BILD, AOR=3.7, 95% CI 1.72 to 8.2), and also severe stage of COVID-19 was associated with hypoalbuminaemia (AOR=3.3, 95% CI 1.4 to 7.9). SARS-COV-2 infection was independently associated with LFT abnormality.

Patients with COVID-19 had decreased albumin levels, and elevated AST, GGT, BILT and BILD levels.

to determine the impact of liver fibrosis on the prognosis of COVID and liver injury associated with the infection.

retrospective multicenter study including 575 patients requiring admission for COVID-19 between January and June 2020. Fibrosis index-4 (FIB-4) was calculated within six months prior to infection and at six months post-infection.

baseline FIB-4 was elevated in patients who died (1.91 ± 0.95 vs 1.43 ± 0.85; p < 0.001). In addition, 17.1 % (32/187) of patients with baseline FIB-4 < 1.45 died vs 52.9 % (9/17) with FIB-4 > 3.25 (p < 0.001). In the adjusted multivariate analysis, baseline FIB-4 (OR 1.61 [95 % CI: 1.19-2.18]; p = 0.002) was independently associated with mortality. Parameters associated with liver injury, including aspartate aminotransferase (AST) (28 ± 10 vs 45 ± 56 IU/l; p < 0.001) and alanine aminotransferase (ALT) (20 ± 12 vs 38 ± 48 IU/l; p < 0.001) were significantly higher at admission compared to baseline. Furthermore, FIB-4 increased from baseline to the time of admission (1.53 ± 0.88 vs 2.55 ± 1.91; p < 0.001), and up to 6.9 % (10/145) of patients with FIB-4 < 1.45 on admission died vs 47.5 % if FIB-4 > 3.25 (58/122) (p < 0.001). In the adjusted multivariate analysis, FIB-4 on admission (OR 1.14 [95 % CI: 1.03-1.27]; p = 0.015) was independently associated with mortality. In addition, AST (42 ± 38 vs 22 ± 17 IU/l; p < 0.001) and ALT (40 ± 50 vs 20 ± 19 IU/l; p < 0.001) were significantly reduced at six months after the resolution of infection. Accordingly, FIB-4 decreased significantly (2.12 ± 1.25 vs 1.32 ± 0.57; p < 0.001) six months after the infection.

increased FIB-4, either at baseline or at the time of admission, was associated with severity and mortality related to respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the liver damage expressed by elevated transaminases and FIB-4 levels was reversible in most of patients.

The limited literature on the clinical course of COVID-19 among patients with underlying liver disease (LD) is available from India. The present study aimed to evaluate the clinical and mutational profile of SARS-CoV-2 among LD cases. This was a retrospective study including admitted LD cases in whom SARS-CoV-2 RT-PCR testing was performed. Complete demographic and clinical details were retrieved from Hospital Information System. Detailed mutational analysis was performed by comparing LD COVID-19 positive study group, i.e. LD-CoV(+) with COVID-19 positive outpatients without any underlying LD as control, i.e. NLD-CoV(+). Out of 232 enrolled LD cases, 137 (59.1%) were LD-CoV(+). LD cases with existing co-morbidities were affected more (P = 0.002) and had 2.29 times (OR 2.29, CI 95%, 1.25-4.29) higher odds of succumbing to COVID-19 (P = 0.006). On multivariate regression analysis, ascites (P = 0.05), severe COVID-19 pneumonia (P = 0.046), and an increased levels of bilirubin (P = 0.005) and alkaline phosphatase (P = 0.003) were found to be associated with adverse outcome in LD-CoV(+).On mutational analysis, we found certain differences between LD- and NLD-CoV(+) infected with Delta [LD- and NLD-CoV (+ /D)] and Omicron [LD- and NLD-CoV(+/O)]. More mutations were shared between LD- and NLD-CoV(+/O) compared to LD- and NLD-CoV(+/D). There were differences in prevalence of indel mutations specific to LD-CoV ( +) for both Delta and Omicron. Moreover, we also reported an interesting genic bias between LD- and NLD-CoV( +) in harbouring deleterious/tolerated mutations. To conclude, LD cases with comorbidities were affected more and had higher odds of mortality due to COVID-19. The definite difference between LD- and NLD-CoV(+) groups with respect to frequency of harboured mutations and an inherent genic bias between them is of noteworthy importance.

Coronavirus disease 2019 (COVID-19) is characterized by an acute respiratory infection with multisystem involvement and the association of its severity to liver function abnormalities is not well characterized. The aim of this study was to assess the association between the severity of COVID-19 patients and liver function abnormalities. This retrospective study included adult patients with confirmed COVID-19, which were classified as non-severe or severe according to World Health Organization guidelines. Liver function test results were compared between the severity groups. A total of 339 patients were included of which 150 (44.25%) were severe cases. The male-to-female ratio was 0.9:1 and 3:2 in the non-severe and severe groups, respectively (p=0.031). Aspartate aminotransferase (AST), alanine transaminase (ALT), and total bilirubin levels and acute liver injury (ALI) incidence were significantly higher in the severe group compared to non-severe group (p<0.001, p<0.001, p=0.025, p=0.014, respectively). In contrast, albumin levels were significantly lower (p=0.001). Multivariate analysis showed that ALI was significantly associated with human immunodeficiency virus (HIV) infection (odds ratio (OR): 5.275; 95% confidence interval (CI): 1.165-23.890, p=0.031), hemoglobin level (OR: 1.214; 95%CI: 1.083-1.361, p=0.001), and hypoalbuminemia (OR: 2.627; 95%CI: 1.283-5.379, p=0.008). Pre-existing liver diseases were present in 6.5% of patients. No significant differences were observed between the groups based on COVID-19 severity and ALI presence. Liver function test abnormalities, including ALI, are more prevalent in patients with severe COVID-19 infection. HIV infection, high hemoglobin levels, and hypoalbuminemia may be potential risk factors for ALI.

Advanced chronic liver disease (ACLD) is associated with a wide spectrum of immune dysfunction. The clinical impact of SARS-CoV-2 on the development of decompensation and immune response in unvaccinated outpatients has not as yet been clearly defined. This study aimed to evaluate the clinical and immunological impact of SARS-CoV-2 on outpatients with ACLD. This is an observational case-control study, in which ACLD outpatients were included prospectively and consecutively and classified into two groups: SARS-CoV-2 infected and non-infected. Patients' baseline characteristics and infection data were collected and analyzed. Immunoglobulin G (IgG) levels against Spike 1 were evaluated. The primary endpoint was risk of liver decompensation during follow-up, assessed after propensity score matching and adjusted by Cox regression. Between October 2020 and July 2021, ACLD outpatients (n = 580) were identified, and 174 patients with clinical follow-up were included. SARS-CoV-2 infection incidence was 7.6% (n = 44). Risk of liver decompensation was significantly higher after infection (HR = 2.43 [1.01-5.86], p = 0.048) vs. non-infection. The time of IgG evaluation was similar in all patients (n = 74); IgG concentrations were significantly higher in compensated vs. decompensated patients (1.02 ± 0.35 pg/mL vs. 0.34 ± 0.16 pg/mL, p < 0.0001) and correlated with hemoglobin levels. The dysregulation of the innate immune response in patients with decompensated liver disease increased the risk of further decompensation following SARS-CoV-2, mainly due to a worsening of ascites.

Hepatic sequelae are frequently reported in coronavirus disease 2019 cases and are correlated with increased disease severity. Therefore, a detailed exploration of host factors contributing to hepatic impairment and ultimately infection outcomes in patients is essential for improved clinical management. The causes of hepatic injury are not limited to drug-mediated toxicity or aberrant host inflammatory responses. Indeed, multiple studies report the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in liver autopsies and the susceptibility of explanted human hepatocytes to infection. In this review, we confirm that hepatic cells express an extensive range of factors implicated in SARS-CoV-2 entry. We also provide an overview of studies reporting evidence for direct infection of liver cell types and the infection-induced cell-intrinsic processes that likely contribute to hepatic impairment.

Specific associations between liver cirrhosis and liver transplant with poorer outcomes in COVID-19 are still not completely clear.

We aimed to evaluate the clinical characteristics and outcomes of patients with severe COVID-19 and cirrhosis or liver transplant in Sao Paulo, Brazil.

A retrospective observational study was conducted in a quaternary hospital. Patients with COVID-19 and liver cirrhosis or liver transplant were selected. The clinical and demographic characteristics, as well as the outcomes, were assessed using electronic records.

A total of 46 patients with COVID-19 and liver condition were included in the study. Patients with liver cirrhosis had significantly more endotracheal intubation and a higher relative risk of death than liver transplant recipients. Patients with higher MELD-Na scores had increased death rates and lower survival probability and survival time.

Patients with liver cirrhosis, especially those with higher MELD-Na scores, had poorer outcomes in COVID-19. Liver transplant recipients do not seem to be linked to poorer COVID-19 outcomes.

Sepsis remains a global health burden associated with significant morbidity and mortality. Bacteria are known to be the predominant pathogens in sepsis; however, viral etiologies in sepsis are still under diagnosed. Respiratory viral pathogens have been previously linked to sepsis, but the knowledge of incidence, disease burden and mortality of viral-induced sepsis remains limited. This study aimed at understanding the role of respiratory viral infections in the causation of sepsis in liver disease patients.

In this retrospective study, the clinical records of liver disease patients with influenza-like illness, whose requests for respiratory viral testing were received from January 2019 to December 2022, were reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics, Utah, USA).

Of 1391 patients tested, a respiratory viral etiology was detected in 23%. The occurrence of sepsis was seen in 35%. Among these, isolated viral etiology with no other bacterial/fungal coinfection was found in 55% of patients. Rhinovirus/Enterovirus was found as the most common underlying viral etiology (23.4%). The sepsis prevalence was higher among patients with associated comorbidities (45%) and decompensated cirrhosis (84%). On multi-variable analysis, no factor was found independently associated with sepsis-related mortality.

This study underlines the importance of isolated viral etiology in causation of sepsis among liver disease patients. Patients with comorbidities, older age and decompensated cirrhosis are at an increased risk of developing sepsis and are associated with poorer outcomes. Accurate and timely identification of the viral etiology in sepsis would prevent the misuse of antibiotics and improve overall patient care.

Vaccines prevent a significant number of deaths annually. However, certain populations do not respond adequately to vaccination due to impaired immune systems. Cirrhosis, a condition marked by a profound disruption of immunity, impairs the normal immunization process. Critical vaccines for cirrhotic patients, such as the hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcal, and coronavirus disease 19 (COVID-19), often elicit suboptimal responses in these individuals. The humoral response, essential for immunization, is less effective in cirrhosis due to a decline in B memory cells and an increase in plasma blasts, which interfere with the creation of a long-lasting response to antigen vaccination. Additionally, some T cell subtypes exhibit reduced activation in cirrhosis. Nonetheless, the persistence of memory T cell activity, while not preventing infections, may help to attenuate the severity of diseases in these patients. Alongside that, the impairment of innate immunity, particularly in dendritic cells (DCs), prevents the normal priming of adaptive immunity, interrupting the immunization process at its onset. Furthermore, cirrhosis disrupts the gut-liver axis balance, causing dysbiosis, reduced production of short-chain fatty acids (SCFAs), increased intestinal permeability, and bacterial translocation. Undermining the physiological activity of the immune system, these alterations could impact the vaccine response. Enhancing the understanding of the molecular and cellular factors contributing to impaired vaccination responses in cirrhotic patients is crucial for improving vaccine efficacy in this population and developing better prevention strategies.

Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class C, are at increased risk of severe coronavirus disease-2019 (COVID-19) upon infection with severe acute respiratory coronavirus 2 (SARS-CoV-2). The biological mechanisms underlying this are unknown. We aimed to examine the levels of serum intrinsic antiviral proteins as well as alterations in the innate antiviral immune response in patients with decompensated liver cirrhosis. Serum from 53 SARS-CoV-2 unexposed and unvaccinated individuals, with decompensated liver cirrhosis undergoing assessment for liver transplantation, were screened using SARS-CoV-2 pseudoparticle and SARS-CoV-2 virus assays. The ability of serum to inhibit interferon (IFN) signalling was assessed using a cell-based reporter assay. Severity of liver disease was assessed using two clinical scoring systems, the Child-Pugh class and the MELD-Na score. In the presence of serum from SARS-CoV-2 unexposed patients with decompensated liver cirrhosis there was no association between SARS-CoV-2 pseudoparticle infection or live SARS-CoV-2 virus infection and severity of liver disease. Type I IFNs are a key component of the innate antiviral response. Serum from patients with decompensated liver cirrhosis contained elevated levels of auto-antibodies capable of binding IFN-α2b compared to healthy controls. High MELD-Na scores were associated with the ability of these auto-antibodies to neutralize type I IFN signalling by IFN-α2b but not IFN-β1a. Our results demonstrate that neutralizing auto-antibodies targeting IFN-α2b are increased in patients with high MELD-Na scores. The presence of neutralizing type I IFN-specific auto-antibodies may increase the likelihood of viral infections, including severe COVID-19, in patients with decompensated liver cirrhosis.